Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma
Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma
复制标题
DOI：
10.1038/modpathol.3800711
复制
发表时间：
2007-01-01
期刊：
影响因子：
7.5
通讯作者：
So, Samuel
中科院分区：
文献类型：
--
作者：
Chua, Mei-Sze;Sun, Hongbo;So, Samuel
肝细胞癌是一种高度致命的癌症，通常预后不良。预后标志物可以帮助其临床管理和了解预后不良的生物学。通过早期的基因表达研究，我们发现N-Myc下调基因1（NDRG 1）在肝细胞癌中的表达显著高于非肿瘤性肝脏。由于NDRG 1是一个分化相关基因，具有公认的转移抑制活性，我们研究了其过表达的临床意义。使用一组独立的患者样本进行的定量实时聚合酶链反应证实，与非肿瘤肝脏样本相比，肝细胞癌中NDRG 1的显著过表达（P < 0.001）。此外，高水平NDRG 1转录物与较短的总生存期（P < 0.001）、晚期肿瘤（P = 0.001）、血管浸润（P = 0.003）、大肿瘤尺寸（P = 0.011）和高Edmondson-Steiner组织学分级（P = 0.005）相关。NDRG 1蛋白在肝细胞癌组织中的表达明显高于非肿瘤性肝组织、肝硬化和良性肝组织（P < 0.001）。NDRG 1蛋白在中、低分化肝癌组织中的表达明显高于高分化肝癌组织（P < 0.005）。此外，与没有血管浸润的肝细胞癌相比，具有血管浸润的肝细胞癌也表达升高水平的NDRG 1蛋白（P < 0.005）。我们的研究结果表明NDRG 1可能是肝细胞癌的肿瘤标志物，其过表达与肿瘤分化、血管浸润和总生存率相关。其在肝细胞癌中的显著升高的表达可能是肿瘤侵袭性和患者预后的有用指标。
Hepatocellular carcinoma is a highly lethal cancer that typically has poor prognosis. Prognostic markers can help in its clinical management and in understanding the biology of poor prognosis. Through an earlier gene expression study, we identified N-Myc downregulated gene 1 (NDRG1) to be significantly highly expressed in hepatocellular carcinoma compared to nontumor liver. As NDRG1 is a differentiation-related gene with putative metastasis suppressor activity, we investigated the clinical significance of its overexpression. Quantitative real-time polymerase chain reaction using an independent set of patient samples confirmed the significant overexpression of NDRG1 in hepatocellular carcinoma compared to nontumor liver samples (P < 0.001). Additionally, high levels of NDRG1 transcript correlated with shorter overall survival (P < 0.001), late tumor stage (P = 0.001), vascular invasion (P = 0.003), large tumor size (P = 0.011), and high Edmondson-Steiner histological grade (P = 0.005). Using immunohistochemistry, NDRG1 protein was found to be significantly overexpressed in hepatocellular carcinoma samples compared to nontumor liver or cirrhotic and benign liver lesions (P < 0.001). Among the hepatocellular carcinoma samples, those which are moderately and poorly differentiated express higher levels of NDRG1 protein than those which are well-differentiated (P < 0.005). Additionally, hepatocellular carcinomas with vascular invasion also express elevated levels of NDRG1 protein compared to those without vascular invasion (significant at P < 0.005). Our results suggest NDRG1 to be a likely tumor marker for hepatocellular carcinoma, the overexpression of which is correlated with tumor differentiation, vascular invasion, and overall survival. Its significantly elevated expression in hepatocellular carcinoma could be a useful indicator of tumor aggressiveness and therefore patient prognosis.